Abstract 6216: Intratumoral B0112 in combination with radiotherapy synergizes to achieve CD8 T cell mediated local tumor control
Authors: Maria.E. Rodriguez-Ruiz, Irantzu serrano, Eneko Garate, Inmaculada Rodriguez, maite alvarez, Carmen Molina, Miguel Fernandez de Sanmamed, Leire Arbea, Marta Moreno, Marisol Quintero, Ignacio Melero
Journal: Cancer Research (2022)

Abstract Background: Radioimmunotherapy combines irradiation of tumor lesions with immunotherapy to achieve local and abscopal control of cancer. Most immunotherapy agents are given systemically, but strategies for delivering immunotherapy locally are under clinical scrutiny to maximize efficacy and avoid toxicity. Local immunotherapy by injecting various patterns of molecules shows efficacy both preclinical and clinically. BO112 is a viral mimetic based on nanoplexed double stranded RNA (poly IC) which exerts immune-mediated antitumor effects in mice and humans upon intratumoral delivery. BO112 and external beam irradiation were used to make the proof-of-concept local immunotherapy plus radiation therapy combinations. Methods: Murine transplantable tumor cells lines (TSA, MC38 and B16 ova) were used to show increased immunogenic features under irradiation as well as bilateral tumor models in which only one of the lesions could be irradiated. Flow cytometry on cell suspensions from tumor draining lymph nodes and multiplex tissue immunofluorescence were used to determine mechanims of antitumor immunity. Depletions of immune cell populations and knock out mice for IFNAAR and BAFT3 genes were used to delineate the immune system requirements for efficacy. Results: In cultures of TSA breast cancer cells the combination of irradiation and BO112 showed more prominent features of immunogenic tumor-cell death including type I interferon reléase. Injection of BO112 in the tumor lesions under radiation achieved excellent control of the treated tumors whilst modest delays in contralateral tumor progression were observed. Local effects were associated with more prominent presence of antitumor CTLs and cDC1 dendritic cells in the tumor and regional lymph nodes. Importantly, local irradiation plus BO112 in a tumor lesion enhanced the therapeutic effect of radiotherapy on distant uninjected tumor lesion. Conclusions: This study demonstrates that local BO112 immunotherapy and external beam radiation therapy can exert synergies to achieve local tumor control. This beneficial effect can be extended to non-injected lesions as long as they are also irradiated, suggesting strategies to treat oligometastatic patients with lesions susceptible to radiotherapy and at least one of them accessible for BO112 repeated intratumoral injections. Citation Format: Maria.E. Rodriguez-Ruiz, Irantzu serrano, Eneko Garate, Inmaculada Rodriguez, maite alvarez, Carmen Molina, Miguel Fernandez de Sanmamed, Leire Arbea, Marta Moreno, Marisol Quintero, Ignacio Melero. Intratumoral B0112 in combination with radiotherapy synergizes to achieve CD8 T cell mediated local tumor control [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6216.